Guanidine and imidazole are important functional molecules that constitute the side chain of basic amino acids (arginine and histidine); these molecules are capable of interacting with mineral surfaces. However, little information is available about the effect of these molecules on mineral dissolution, including amorphous silica. In this study, to evaluate the effect of these organic molecules on the dissolution rates of amorphous silica, dissolution experiments were performed in solutions containing these molecules and other related heterocyclic compounds. The dissolution experiments were conducted by the batch method using 0.1 g of amorphous silica and 100 mL of 0.1 mM NaCl solution with 0.0, 0.1, 1.0, and 10.0 mM of guanidine, imidazole, pyrazole, or pyrrole at pH values of 4, 5, and 6. The results demonstrated that these compounds can enhance the dissolution rate of amorphous silica, depending on their ionic speciation in the following order: guanidine = imidazole > pyrazole > pyrrole. When 10.0 mM solutions were used, both guanidine and imidazole greatly increased the dissolution rate with an enhancement factor of 5.5–6.5, pyrazole exhibited a smaller change in the dissolution rate with an enhancement factor of 1.5–2.4, and pyrrole exhibited no significant enhancement. ChemEQL calculations confirmed that guanidine (pK = 13.6) and imidazole (pK = 6.99) are fully protonated and mostly present as cationic species in a pH range of 4–6; therefore, these compounds are capable of interacting with the >SiO− sites of amorphous silica. Pyrazole (pK = 2.61) and pyrrole (pK = 0.4), however, existed mostly as neutral forms. The concentrations of cationic species of pyrazole and pyrrole were at least one and three orders of magnitude lower than those of fully protonated compounds, respectively; therefore, pyrazole and pyrrole were less reactive than the fully protonated compounds on the surfaces of amorphous silica.